The germ cell lineage ensures the continuity of life through the generation of male and female gametes, which unite to form a totipotent zygote. Germ cell specification and development are vital in reproduction and heredity. In mice, primordial germ cells (PGCs), precursors both for spermatozoa and oocytes, arise in the epiblasts in response to cytokines, including, most importantly, bone morphogenetic protein 4 (BMP4), from extraembryonic tissues (non-patent documents 1 and 2). We have recently established a culture system to induce embryonic stem cells (ESCs)/induced pluripotent stem cells (iPSCs) into epiblast-like cells (EpiLCs) using cytokines including activin A (ActA) and basic fibroblast growth factor (bFGF), and then into primordial germ cell-like cells (PGCLCs) using cytokines including BMP4 (patent document 1, non-patent documents 3 and 4). Male and female PGCLCs bear full potential for spermatogenesis and oogenesis, and thus may have potential for unveiling the mechanism of and regulating the germ-cell specification pathway and subsequent development in vitro (patent document 1, non-patent documents 3 and 4).
In replace of cytokines, forced expression of exogenous transcription factors (TFs) may activate endogenous key transcription circuitry for PGC specification. However, our previous studies revealed that PGC specification involves complex regulation of a large number of genes, while some key TFs were identified (non-patent document 5). Accordingly, the TFs sufficient for the induction of germ cell fate and the precise mechanism of action of key TFs remain unknown.